- Process for preparing 1,3-dialkyl-5-hydroxyoxindoles and the ether derivatives thereof
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The invention is directed to a process for preparing a 1,3-dialkyl-5-hydroxyoxindole of formula 1: STR1 comprising heating an N-alkyl-p-alkoxy-(α-haloacyl)anilide of formula 2: STR2 wherein the substituents are as defined herein, in the presence of an anhydrous zinc halide to a temperature in the range from about 120° C. to about 160° C., and isolating the 1,3-dialkyl-5-hydroxyoxindole prepared.
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- Process for the enantioselective synthesis of intermediates used in the preparation of physostigmine
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This invention relates to a process of obtaining optically pure enantiomers of an alkylated oxindole selected from STR1 where R is methyl, ethyl or benzyl.
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- Process for the enantioselective synthesis of intermediates used in the preparation of physostigmine
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A process for the stereoselective synthesis of [R]- and [S]-2,3-dihydro-1,3-dimethyl-2-oxo-1H-indole-3-acetonitriles comprises reacting racemic and 5-alkoxy-substituted (±)-1,3-dimethyloxindoles with a halogenated acetonitrile in the presence of a substituted N-benzyl cinchoninium, quinidinium, cinchonidinium, or quininium catalyst. The resulting alkylated oxindoles can be converted to primary amines by catalytic reduction in the presence of hydrogen gas. One of the primary amines, such as enantiomers of 3-(2-aminoethyl)-1,3-dihydro-1,3-dimethyl-5-methoxy-2H-indol-2-one, can be enriched by contact with a chiral tartaric acid in an amount sufficient to preferentially precipitate a salt of the chiral acid and one of the enantiomers. The product can be used in the synthesis of stereospecific forms of physostigmine and related compounds having pharmaceutical activity.
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